Biomedical subjects
C Gross
Publications and source records attributed to C Gross.
The incidence of thrombovenous and thromboembolic complications in kidney transplant patients with recurrent glomerulonephritis is dependent on the occurrence of severe proteinuria.
BACKGROUND: Patients with recurrent glomerulonephritis (RG) after kidney transplantation are at high risk for thromboembolic events but it is unclear when the risk begins to increase. PATIENTS AND METHODS: We evaluated the risk for thrombovenous and thromboembolic complications in relation to the occurrence of severe proteinuria (> or = 2 g protein in 24-hour urine) in 15 renal allograft recipients with biopsy-proven RG, who had received 20 allografts RG. The total period of observation was 53 (10-91) months. The post-transplant period before the occurrence of severe proteinuria lasted 18 (1-34) months and the subsequent proteinuric period until the end of the study, 35 (9-85) months. RESULTS: The monthly incidence of thrombovenous and thromboembolic complications was only 1/18 in the first period before and in contrast, 11/35 in the subsequent period after the occurrence of severe proteinuria. The mean urinary protein excretion increased from 0.4 +/- 0.1 g/day immediately after transplantation to 6.1 +/- 4.8 g/day at the end of the study (p < 0.001). During the same period there was a 1.2-fold increase of fibrinogen (from 366 +/- 88 to 442 +/- 120 mg/dl, p < 0.025) and a 1.2-fold decrease of antithrombin III (from 110 +/- 12 to 92 +/- 12%, p < 0.001). All thrombotic complications occurred in 6 patients with 9 grafts; at the end of the study this group showed higher fibrinogen concentrations (454 +/- 155 versus 433 +/- 89 mg/dl, NS) m and lower antithrombin III levels (88 +/- 11 versus 97 +/- 11%, p < 0.05) than the group without thrombotic complications. CONCLUSION: In kidney transplant patients with RG a high risk for thrombovenous and thromboembolic complications can be obs- served after the occurrence of severe proteinuria; this can mainly be explained by high fibrinogen and low antithrombin III levels. Anticoagulation therapy should be started in patients with RG immediately after the occurrence of severe proteinuria.
Reorganization of area 5 neuron activity in trained deafferented monkeys.
A command function is attributable to certain area 5 neurons which clearly fire before movement in trained monkey. Statistical analysis allowed us to define two categories of spontaneous firing mode for these cells: type I which exhibits a random pattern of discharge (14%), and type II displaying markedly "bursty firing". After deafferentation, both categories were still observed in the same proportion. However, the discharge pattern and frequency in type II cells remained altered for 5 months. This paralleled rises in neural latency response (RS) and reaction time (RT). Beginning the 6th month, there was a progressive reorganization of the spontaneous activity along with normalization of RS and RT. Our results support the idea that an enhancement of the excitability of these area 5 neurons, initially depressed by the suppression of sensory inputs, occurs over time. This sensitivity gain could be due to neural network rearrangements induced by repetitive operant solicitation.
[Squamous cell carcinoma developing from epidermodysplasia verruciformis].
We report on a 50-year-old man who presented with squamous cell carcinoma of the forehead skin developing from epidermodysplasia verruciformis (EV). EV is an uncommon disease characterized by flat warts or scaling macules resembling pityriasis vericolor on sun-exposed skin. Histogenetic predisposition and human papilloma virus infection play a part. As shown in our case there is, depending on HPV subtype and additional exposure to ultraviolet light, a high risk of malignant transformation. These patients require close monitoring.
[Restrictive dermopathy].
Restrictive dermopathy is a rare, fatal, autosomal recessive, congenital skin disease. Rigidity of translucent thin skin, which is thus highly vulnerable and tears, spontaneously causes intra-uterine fetal akinesia or hypokinesia deformation sequence (FADS), characteristic dysmorphic facies with fixed open mouth in O position, and generalized joint contractures (arthrogryposis). Polyhydramnios and pulmonary hypoplasia are distinctive manifestations, leading to respiratory insufficiency and premature delivery at about 31 weeks of gestation. We report on a case of a prematurely born infant who presented with the typical morphological features and describe the light- and electron-microscopical findings as described in the literature.
Aortic valve replacement: is the stentless xenograft an alternative to the homograft? Midterm results.
BACKGROUND: This study was performed to assess the midterm clinical results after aortic valve replacement (AVR) with stentless xenograft (SX) compared with cryopreserved aortic or pulmonary homografts (HX). METHODS: In 139 patients (<60 years) undergoing elective AVR, 59 HX and 80 SX were inserted. All patients were followed clinically and by color flow Doppler echocardiography for 45+/-12 months (range 31-58 months). RESULTS: There were 5 in-hospital deaths (3.5%): 4 HX and 1 SX (p = NS). The mean gradient was 6+/-2 mm Hg in HX versus 13+/-6 mm Hg in SX (p<0.001) and remained unchanged during follow-up. Actuarial survival (HX 77%, SX 80%), freedom from endocarditis (HX 91%, SX 99%), freedom from thromboembolic events (HX 98%, SX 90%), and freedom from reoperation (HX 98%, SX 100%) were comparable between groups after 58 months. CONCLUSIONS: Despite slightly higher transvalvular gradients, the stentless aortic valve achieved excellent midterm results, when compared with homografts.
Relationships between aggressive behavior in cognitively impaired nursing home residents and use of restraints, psychoactive drugs, and secured units.
This study examined relationships between aggressive behavior in cognitively impaired nursing home residents and physical restraints, psychoactive drugs, and placement on a secured unit. Data were obtained from 116 residents who were consistently aggressive as measured by the Ryden Aggression Scale 2. Subjects averaged 9.5 aggressive behaviors per day. Forty-seven percent of subjects were restrained, and 62% were regularly receiving psychoactive drugs. Use of restraints, antipsychotics, and placement on a secured unit were all significantly related to increased physical aggression scores. Four variables accounted for 23% of the variance in physical aggression scores: location on a secured unit, not receiving an antidepressant, being restrained, and number of psychotropic and/or anxiolytic medications administered. Significantly lower physical aggression scores were noted for subjects receiving antidepressants.
Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors.
Dysfunctions of the serotonergic system have been implicated in a number of psychiatric disorders including depression, anxiety and disorders of impulse control. To model these disorders we have generated mice with altered serotonergic systems. Specifically, we have created mice that lack or express reduced levels of two serotonin receptors: 5-HT1A and 5-HT1B receptors. These receptors are localized both on serotonergic neurons where they act as autoreceptors and on non-serotonergic neurons. As a result, the 5-HT1A and 5-HT1B receptors control the tone of the serotonergic system and mediate some of the postsynaptic effects of serotonin. Agonists of these receptors are currently used in the treatment of migraine and anxiety disorders. Mice lacking these receptors develop, feed, and breed normally and do not display any obvious abnormalities. However, when analyzed in a number of behavioral paradigms, the 5-HT1A and 5-HT1B knockout mice display a number of contrasting phenotypes. While the 5-HT1B knockout mice are more aggressive, more reactive, and less anxious than the wild-types, the 5-HT1A knockouts are less reactive, more anxious, and possibly less aggressive than the wild-types. We are currently investigating with tissue-specific knockout mice which neural circuits are responsible for these phenotypes.
Midterm results after aortic valve replacement with the autologous tissue cardiac valve.
OBJECTIVE: To assess midterm results after aortic valve replacement (AVR) with an autologous tissue cardiac valve (ATCV). This new technique was developed to construct a tissue prosthesis for AVR using the patients pericardium, harvested at the time of operation with negligible effect on operating time. METHODS: Briefly, glutaraldehyde tanned pericardium is mounted on a stent requiring no suturing. Between March 1994 and December 1996, 87 patients, 44/43 M/F and aged 70 +/- 6 years had AVR for aortic stenosis (80%), aortic insufficiency (6%) and combined lesions (14%), one patient suffered from endocarditis. Additional coronary artery bypass was done in 25%, aortic root enlargement in 7%. Aortic cross clamp and cardiopulmonary bypass times were 69 +/- 21 and 93 +/- 29 min. All patients were followed by clinical examination and color flow Doppler echocardiography in 3-12 months interval. Follow up was 99% complete. RESULTS: There were five perioperative deaths (6%), none of them valve related. Eighty-one patients were followed up to a period of 52 months (mean interval 37.5 +/- 1.3 months), one patient was lost for follow up. Overall survival was 86, 81, 79 and 71% at 12, 24, 36 and 48 months, respectively. There were 14 late deaths with eight (10%) valve related (four cerebral deaths, four sudden deaths). Sixteen patients (20%) had to be re-operated due to severe valve incompetence. Freedom from reoperation was 98, 97, 90 and 63% at 12, 24, 36, and 48 months, respectively. Valve incompetence occurred suddenly, without previous signs in the follow-up examinations. Selection and preparation of the pericardium, the way of fixation of the tissue--brief immersion in glutaraldehyde--and engineering problems might be responsible for this disastrous outcome. CONCLUSION: Due to these results we must state, that the ATCV did not fulfill our expectations and presently we can not recommend it as an aortic valve substitute.
Trichloroethylene and parkinsonism: a human and experimental observation.
This report describes the case of a 47-year-old woman who developed Parkinson's disease after seven years of professional exposure to trichloroethylene. In the light of this clinical report, mice were intoxicated with trichloroethylene and tyrosine hydroxylase immunoreactivity was used to measure neuronal death in the substantia nigra pars compacta. Treated mice presented significant dopaminergic neuronal death in comparison with control mice (50%). The environmental trichlorethylene pollution, as well as other unspecific neurotoxic solvents, could potentially contribute to the genesis of some cases of Parkinson's disease.
Cortical stimulation and epileptic seizure: a study of the potential risk in primates.
OBJECTIVE: The recent successful development of chronic stimulation of the motor cortex as a treatment for neuropathic and central pain does not exclude the possibility of eventual side effects, such as epileptic seizure or a lowering of the epileptic threshold. This study evaluates the behavioral and electroencephalographic impact of this treatment in three normal monkeys. RESULTS: None of the monkeys presented epileptic behavior or abnormal electroencephalographic activity at parameters of stimulation currently used in clinical series, i.e., frequency and pulse duration of approximately 40 Hz and 90 microseconds, respectively, and an intensity just under the threshold for inducing muscle twitch in painful areas. Higher intensities did, however, induce reversible epileptic seizure. There was, nonetheless, no modification of the epileptic threshold, because even after these seizures, intermittent light stimulation elicited no abnormal electroencephalographic activity. CONCLUSION: It thus seems that motor cortex stimulation does not induce epileptic complications when the classic clinical criteria of stimulation are respected. Nevertheless, it would be wise to subject candidates for implantation to intermittent light stimulation before and after a period of stimulation to ascertain the innocuousness of the cortical stimulation.
Identification of a contact site for different transcription activators in region 4 of the Escherichia coli RNA polymerase sigma70 subunit.
The sigma subunit of RNA polymerase orchestrates basal transcription by first binding to core RNA polymerase and then recognizing promoters. Using a series of 16 alanine-substitution mutations, we show that residues in a narrow region of Escherichia coli sigma70 (590 to 603) are involved in transcription activation by a mutationally altered CRP derivative, FNR and AraC. Homology modeling of region 4 of sigma70 to the closely related NarL or 434 Cro proteins, suggests that the five basic residues implicated in activation are either in the C terminus of a long recognition helix that includes residues recognizing the -35 hexamer region of the promoter, or in the subsequent loop, and are ideally positioned to permit interaction with activators. The only substitution that has a significant effect on activator-independent transcription is at R603, indicating that this residue of sigma70 may play a distinct role in transcription initiation.
Application of mRNA differential display to investigate gene expression in thermotolerant cells of Saccharomyces cerevisiae.
We have described the use of differential display of PCR-amplified reverse transcribed mRNA (DDRT-PCR) to survey changes in gene expression profiles induced by heat shock and carbon catabolite derepression in Saccharomyces cerevisiae. It is well established that either of these states elicits thermotolerant phenotypes. An initial analysis conducted on cells of an inherently thermosensitive strain (Ysen) indicated that approximately 10% of the total number of cDNAs detected were either up or down regulated following heat shock at 37 degrees C (30 min) in comparison to control cells (25 degrees C). In addition, whereas 7% of all PCR products were preferentially expressed during derepressive growth, approximately 2% were found to be common to both heat-shocked and derepressed cells. A repeat analysis, performed on all three cell types of Ysen as well as cells of a relatively thermoresistant strain (Yres) yielded 30 differentially displayed cDNA fragments common to heat-shocked and derepressed cells of both strains. Eighteen of these generated signals on Northern blots, of which three were confirmed as regulated. Five amplicons, including one not detected by Northern analysis and another from the derepressed state, were cloned and sequenced. Three of these exhibited homology to S. cerevisiae genes with well-characterized protein products: HSP 90, HXK1 and STA1. The remaining two applicons showed nucleotide identity to YTIS11, a homolog of the mammalian TIS11 and putative transcriptional activator, and an orphan gene encoding a hypothetical transmembrane protein belonging to the multi-drug resistance translocase family. Our novel application of DDRT-PCR has identified new and known genes that may be further evaluated as factors involved in stress regulation and has demonstrated the potential of the technique to systematically analyse gene expression in yeast.
Effects of L-DOPA on neuronal activity of the globus pallidus externalis (GPe) and globus pallidus internalis (GPi) in the MPTP-treated monkey.
We studied the effects of L-DOPA on the firing patterns of pallidal neurons in experimental parkinsonism. After a unilateral injection of MPTP, we observed a decrease in the firing rate of GPe neurons, and a slight increase in their bursting activity. In the GPi, there was a considerable augmentation of both neuronal firing frequency and the number of bursting cells. During l-DOPA treatment (10 mg/kg), GPe neurons.pattern is almost unmodified. The firing frequency of GPi neurons, on the contrary, decreased even lower than the control level. A slight reduction was observed in bursting activity. These unexpected results would show that the normalizing effect of L-DOPA on GPi output is limited.
Vitamin D receptor gene polymorphisms: analysis of ligand binding and hormone responsiveness in cultured skin fibroblasts.
Recent reports have suggested that polymorphisms in the gene encoding the vitamin D receptor (VDR) determine a portion of the genetic contribution to bone mineral density (BMD). Individuals homozygous for the allele lacking the Bsm I restriction site in the intron between exons 8 and 9 (BB genotype) have been found to have lower BMD than individuals homozygous for the allele having the Bsm I site (bb genotype). Interestingly, this polymorphism has also been associated with prostate cancer risk. The observed changes in BMD and prostate cancer risk might be due to an alteration in the function or abundance of the VDR leading to differential responsiveness of target cells to the action of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. To test this hypothesis, we cultured dermal fibroblasts from donors with BB, Bb, and bb genotypes and determined the level of VDR expression and the cellular responsiveness to 1,25(OH)2D3 treatment. VDR abundance, affinity for [3H]1,25(OH)2D3, and VDR mRNA levels were not detectably different in BB cells compared to bb cells. Moreover, equal expression of both VDR gene alleles was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) on mRNA from Bb fibroblasts. Fibroblast responsiveness to 1,25(OH)2D3, assessed by induction of 24-hydroxylase mRNA, was similar between BB and bb cell types in dose-response experiments. Although there were individual variations in the parameters we measured, there were no detectable or consistent differences in mean values from our small sample of cultured dermal fibroblasts. In conclusion, we did not detect significant differences in VDR properties or cellular responsiveness to 1,25(OH)2D3 that correlated with VDR genotype. Our findings suggest that these polymorphisms do not affect VDR function, but rather may be a marker for a nearby gene that is responsible for the genotype-associated variation in osteoporosis and prostate cancer risk.
Cell cycle regulated promoters for the targeting of tumor endothelium.
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Aortic homografts versus mechanical valves in aortic valve replacement in young patients: a retrospective study.
BACKGROUND: Whether aortic homografts (AH) or mechanical devices (MD) are the valves of choice for aortic valve replacement in young patients (age 20 to 50 years) is unclear. Hence, we examined all aortic valve replacements performed with AH and MD in a retrospective study. METHODS: Between 1988 and 1995, 45 patients (mean age, 38.6+/-8.5 years) underwent aortic valve replacement with an AH and 40 patients (mean age, 42.0+/-7.2 years) with an MD. Patients' demographic data were comparable in all respects, except acute endocarditis, which was an absolute indication for the use of an AH. RESULTS: The mean follow-up time was 51.7+/-22.6 months for AH versus 44.6+/-26.9 months for MD (not significant). There were significant differences in postoperative outcome among the two groups (p < or = 0.05): perioperative death (4 versus 0 for AH and MD, respectively); reoperation (8 for AH versus 0 for MD); and endocarditis (5 versus 0 for AH and MD). There were higher incidences of embolism (2 versus 0) and hemorrhage (2 versus 0) in MD compared with AH. Only late death was comparable among the two groups with 5 patients in each group. CONCLUSIONS: The mechanical valves in our midterm follow-up are superior to homografts. However, embolic and hemorrhagic complications in MD are continuously impending and cumulative during a long-term follow-up. The surprisingly high rate of endocarditis in the AH group is only partly caused by the indication: 2 cases were recurrent, but there were also 2 new onsets of endocarditis. In 4 cases structural deterioration was responsible for reoperation. Aortic valve replacement with aortic homografts showed a rather unfavorable midterm outcome in this selected group of young patients. A surprisingly high rate of graft endocarditis and structural deterioration led to subsequent reoperations. Although our results with mechanical valves are satisfying, embolism and hemorrhage are impending risk factors for many years to come in these young patients.